Identification of Chromosomal Regions Linked to Autism-Spectrum Disorders: A Meta-Analysis of Genome-Wide Linkage Scans

Abstract

Background: Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of pervasive neurodevelopmental disorders with a strong hereditary component. Although, genome-wide linkage scans (GWLS) and association studies (GWAS) have previously identified hundreds of ASD risk gene loci, the results remain inconclusive. Method: We performed a heterogeneity-based genome search meta-Analysis (HEGESMA) of 15 genome scans of autism and ASD. Results: For strictly defined autism, data were analyzed across six separate genome scans. Region 7q22-q34 reached statistical significance in both weighted and unweighted analyses, with evidence of significantly low between-scan heterogeneity. For ASDs (data from 12 separate scans), chromosomal regions 5p15.33-5p15.1 and 15q22.32-15q26.1 reached significance in both weighted and unweighted analyses but did not reach significance for either low or high heterogeneity. Region 1q23.2-1q31.1 was significant in unweighted analyses with low between-scan heterogeneity. Finally, region 8p21.1-8q13.2 reached significant linkage peak in all our meta-Analyses. When we combined all available genome scans (15), the same results were produced. Conclusions: This meta-Analysis suggests that these regions should be further investigated for autism susceptibility genes, with the caveat that autism spectrum disorders have different linkage signals across genome scans, possibly because of the high genetic heterogeneity of the disease. © Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.